Older age (>70) is an independent risk factor for postoperative complications and mortality. However the nature of age's contribution to postsurgical complications remains unclear. One hypothesis is that older patients are more susceptible to the sequelae of pathologic stress. Published data suggest that a relatively new anesthesia technique is associated with superior control of the stress response. This technique eschews the traditional use of inhalational gas (e.g. ether, isoflurane, sevoflurane) in favor of intravenous medications (total intravenous anesthesia, TIVA). This has only been possible in the past several years when the development of improved medications (e.g. propofol) has made it possible to conduct an anesthetic without gas. It is well established that TIVA is associated with a lesser activation of the stress response as evidenced by serum cortisol, lower plasma levels of norepinephrine (NE), epinephrine (E), and growth hormone (GH), and lesser heart rate variability (HRV). If the use of TIVA effectively suppresses the stress response in older adults, then anesthesiologists will leverage this effect to produce better postoperative outcomes. In the context of a GEMSSTAR award, we propose a prospective pilot study to clarify the relationship between anesthetic technique, postsurgical outcomes and a unique set of mRNA markers of perioperative stress in patients >70 years old undergoing TIVA vs. those who are exposed to gas. From published data and experience through my research group's current clinical trial, we have evidence to suggest that TIVA may be a superior technique in older patients. In addition our group has worked closely with the Neurobiology of Aging laboratory at Mount Sinai to identify 9 oxidative stress genes that completely discriminate between immediate pre- and postsurgical patients. We suggest that the mRNA of these genes may be specific biomarkers of patients who are particularly at-risk of perioperative complications. Our hypotheses: 1) Patients undergoing general anesthesia with TIVA will have better outcomes than patients who receive inhalational anesthesia. 2) Patients undergoing general anesthesia with TIVA will have less stress, induction of the oxidative damage response, and immunosuppression than patients who receive inhalational anesthesia. This project is significant because it utilizes innovative biomarkers of stress and is the first study to propose a comparison of an alternative to potentially neurotoxic gas anesthesia in the elderly. The results from this study will form the basis for larger comparative effectiveness trials of anesthetic technique and outcomes in the elderly. PUBLIC HEALTH RELEVANCE: Elderly surgical patients experience disproportionately high perioperative morbidity and mortality even after adjusting for preoperative comorbidities and procedure type. The higher incidence of complications results in longer hospital stays and greater median hospital cost, many of which are not reimbursable under the new Centers for Medicare and Medicaid Guidelines. Discovery of the physiologic mechanism of this underlying susceptibility and a mitigating anesthetic technique would have a large scale impact on the elderly surgical population and society as a whole.